Pneumocystis Pneumonia (PCP)

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Pneumocystis pneumonia, or PCP, is a life-threatening lung disease caused by an organism called Pneumocystis jiroveci (until a few years ago, the organism Pneumocystis carinii was believed to be the cause of PCP in humans). This organism can also infect and cause disease in other organs, including the skin (extrapulmonary Pneumocystis infection). Pneumocystis jiroveci (yee-row-vet-zee) is abundant in the environment. Most healthy people have antibodies to fight this organism every time it enters the body. However, in people with compromised immune systems—such as people with AIDS and those receiving chemotherapy for cancer—antibody responses to Pneumocystis jiroveci fade, rendering them susceptible to PCP.

During the early years of the AIDS epidemic, PCP occurred in more than 80 percent of people living with HIV. It was also highly fatal. However, drugs to prevent PCP have drastically decreased these rates, and these drugs are now recommended for all HIV-infected people who see their CD4 cell count drop below 200.

PCP is preventable.

What are the symptoms, & how is it diagnosed?

Fever is a main symptom of PCP, along with a dry cough that doesn’t produce any phlegm (sputum). Other chief symptoms include chest tightness and difficulty breathing. Fatigue and night sweats can also occur, often before breathing difficulties appear. These are also symptoms of other types of infections, thus it is important to diagnose PCP carefully.

There is no blood test to determine if PCP is present in the body. To diagnose PCP, fluid (sputum) or tissue from the lungs is collected by a doctor and examined by a laboratory under a microscope. While X-rays can be used to determine how much fluid has collected in the lungs, they can’t tell the difference between PCP and other lung infections like tuberculosis.

How is PCP treated?

The most effective treatment for PCP is a combination of two drugs: trimethoprim and sulfamethoxazole (TMP-SMX; Bactrim, Septra). Dosages for both drugs are lower today than they were ten years ago. These drugs can be taken either by mouth in pill form or by intravenous (IV) infusion. People with moderate to severe PCP should also begin taking a corticosteroid like prednisone within 72 hours of beginning treatment with TMP-SMX.

To treat PCP, TMP-SMX must be taken every day for approximately three weeks. After the infection has cleared, patients will need to take lower doses by mouth either once a day or three-times weekly to prevent it from returning.

Unfortunately, between 25 and 50 percent of HIV-positive people are allergic to the sulfur in sulfamethoxazole. Two of the main symptoms seen in people with allergic reactions to SMX are fever and rash. Very often, the allergy can be so severe that people need to stop taking SMX.

For patients who cannot tolerate SMX, the following treatments can be prescribed. While TMP-SMX is clearly the best treatment to choose from, these treatments have been shown to be effective:

Pentamidine: To treat PCP, pentamidine is administered through an IV line every day for three weeks. Generally speaking, intravenous pentamidine should be the second choice for the treatment of severe PCP, if TMP-SMX cannot be taken.

Clindamycin-primaquine: This dual-combination of drugs is usually taken by mouth for three weeks. Clindamycin-primaquine has been shown to be effective for the treatment of mild-to-moderate PCP. For severe cases of PCP, clindamycin can be administered through an IV line (primaquine must still be taken by mouth).

Trimethoprim (TMP)-dapsone: Both of these drugs are taken by mouth for three weeks. While it is not as effective for the treatment of severe PCP, TMP-dapsone appears to be just as effective as TMP-SMX, possibly with fewer side effects, for the treatment of mild-to-moderate PCP. However, TMP-dapsone is considered to be less convenient than TMP-SMX, given that a larger number of pills need to be taken every day.

Trimetrexate-leucovorin: Trimetrexate is administered by IV while leucovorin is taken by mouth. After the three-week treatment schedule has finished, leucovorin will need to be taken for an additional three days to help counter the side effects of trimetrexate. This regimen is considered to be less effective than TMP-SMX, but can be used if TMP-SMX cannot be tolerated.

Aerosolized pentamidine (NebuPent): While this therapy has been used to treat PCP in the past, it is no longer recommended. The above listed drug combinations are believed to be more effective that aerosolized pentamidine. Plus, patients treated with aerosolized pentamidine are more likely to experience a relapse of PCP, compared to those who take the recommended oral or intravenous drug combinations.

Prednisone: By itself, prednisone is not a treatment for PCP. It is a powerful drug that can help control symptoms of PCP, especially for those with severe disease. Patients usually take 40 mg of the drug for five days and then drop the dose to 20 mg a day until PCP therapy is completed.

Can PCP be prevented?

Yes, it can. As with the treatment of PCP, TMP-SMX (Bactrim, Septra) is the most powerful drug to prevent PCP from occurring in the first place. Preventing an infection such as this is known as “prophylaxis.” Initially, one double-strength tablet of TMP-SMX every day in patients with less than 200 T-cells was the recommended dose. Today, many health care providers recommend one single strength tablet once daily or one double-strength tablet be taken three times a week instead. It’s just as effective.

As discussed above, many patients have a hard time handling TMP-SMX due to allergic reactions. There are two options: to switch to an alternative prophylaxis (discussed below) or undergo a process called desensitization. In TMP-SMX desensitization, the goal is to teach your body to get used to the drugs. To do this, your doctor can start you on tiny doses of the drug, using the pediatric liquid formula, and increase it gradually over a few days or over a few weeks. This has been shown to be very successful.

If an alternate PCP prophylaxis is necessary, three options are: aerosolized pentamidine (NebuPent), dapsone, and atovaquone (Mepron). Aerosolized pentamidine is administered using a machine called a nebulizer. This turns the pentamidine liquid into a fine mist that is inhaled. Aerosolized pentamidine must be administered once a month. Dapsone is a tablet, usually taken once a day, sometimes in combination with other antibiotics. Mepron is a creamy liquid that must be taken every day. It should be taken with fatty food in order to be absorbed properly into the bloodstream. Unfortunately, none of these three antibiotics are as effective as TMP-SMX for the prevention of PCP, but do offer a significant benefit.

For HIV-positive people who once saw their CD4 cell count fall below 200, only to see it increase above this level due to antiretroviral therapy, stopping PCP prophylaxis is an option. In general, patients should work closely with their doctors to make sure that their CD4 cell counts are, in fact, above 200 and do not show any sign of decreasing below this level again in the immediate future. If the CD4 cell count falls below 200 again, PCP prophylaxis must be restarted.

Are there any experimental treatments?

If you would like to find out if you are eligible for any clinical trials that include new therapies for the treatment or prevention of PCP, visit ClinicalTrials.gov, a site run by the U.S. National Institutes of Health. The site has information about all HIV-related clinical studies in the United States. For more info, you can call their toll-free number at 1-800-HIV-0440 (1-800-448-0440) or email contactus@aidsinfo.nih.gov.

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